It is often necessary or desirable in determining and evaluating the condition of a patient to determine the concentration of certain electrolytes in the patient's system. Typically, the presence and concentration of electrolytes is determined by analyzing a sample of whole blood or blood serum taken from the patient. Common electrolyte components of interest include potassium, sodium, chloride, carbon dioxide, lithium, ammonium, and pH, to name a few.
Traditionally, such electrolytes have been detected and measured using flame spectrophotometric techniques. Generally, in flame spectrophotometry, a chemical composition is prepared from a sample containing the electrolyte or electrolytes of interest. The composition is then combusted and optical measurements of the resulting flame are made. The spectral characteristics of the flame are then analyzed to determine the presence and concentration of the electrolytes of interest in the sample. The value of flame spectrophotometric techniques is limited by their ability to operate on serum only and not whole blood. In addition, in flame spectrophotometry, it is critical but very difficult to precisely control the combustion of the prepared compound. Consequently, this technique is operator intensive and it is typically not possible to obtain a high degree of repeatability.
In order to overcome the drawbacks and limitations associated with traditional flame spectrophotometric techniques, ion selective electrode apparatus and measuring techniques have been developed. Ion Selective Electrodes (ISE) are devices used to generate an electrical signal (typically a potential) in proportion to the concentration of an electrolyte in a sample such as whole blood. A typical potassium sensitive ISE system is constructed of a pair of electrochemical half-cells. One half-cell, the ISE sensor, generally consists of an electrode and a membrane separated by a fill solution of known potassium concentration. The membrane has an affinity for potassium ions and is typically made from an ion-sensitive polymeric composition. When the half-cell membrane is brought in contact with a sample, the membrane forms a very specific complex with the potassium ions in the sample and, as a result of the accumulated cations, develops a potential across the membrane that is proportional to the unknown potassium concentration in the sample. This relationship closely follows the Nernst equation as is well known in the art. Therefore by knowing the ion concentration on the fill solution side of the membrane and measuring the potential across the membrane, it is possible to calculate the unknown ion concentration on the opposite side of the membrane. A second half-cell, optimized to generate a negligible potential, completes the circuit through the ISE system.
Centrifugal-type analyzers are used to perform a variety of clinical tests on a fluid sample such as whole blood. One such analyzer is fully described in the article by Schultz, et al., entitled "Two Dimensional Centrifugation for Desk Top Clinical Chemistry", Clinical Chemistry, 31/9, pp. 1457-1463 (1985). The analyzer uses centrifugal force to separate serum or plasma from whole blood and measure reagent and plasma volumes. The device is based on a two-dimensional centrifugation process in which a multi-chamber plastic test cartridge containing the sample is centrifuged at 500 times G in two planes oriented at right angles to each other.
Known ISEs are often too large and heavy to fit into the test cartridge of conventional centrifugal-type analyzers. Alternatively, they require several additional solutions for proper operation or have a mechanical configuration that prohibits user replacement.
Accordingly, it is an object of this invention to provide an ISE of sufficiently small size and configuration to allow placement of the ISE within the test cartridge of a conventional centrifugal-type analyzer. It is another object of this invention to provide such an ISE which is a self-contained system, while allowing for user replacement of ISE parts. A further object of the present invention is to provide a mechanical contact that not only holds the ISE in the test cartridge but also provides electrical connection between the ISE and the test cartridge. A further object of the present invention is to provide fill solutions and storage solutions of a composition similar to that of the sample of interest, in order to help prevent drift of the ISE generated potential, and help establish a chemical equilibrium during storage. An even further object of the present invention is to provide a miniaturized screw-in ISE for use in the multichamber test cartridge of a two-dimensional centrifugal analyzer.